Most Genetic Epidemiology Branch investigations evaluate the contributions of host susceptibility and environmental exposure in the development of cancer. In family studies, the host susceptibility measure is frequently an alteration in specific gene(s). These studies tend to be very long term with varying activity. Although two genes associated with melanoma susceptibility have been identified (CDKN2A and CDK4), alterations in these genes are found in only a small percentage of melanoma-prone families. The search for other genes continues in collaboration with an international consortium. we continue to accrue and evaluate new families. Genetic analyses of Italian melanoma families continue with a whole genome search for susceptibility loci. A pilot study is underway to assess the accrual of new Italian melanoma-prone families. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include additional families. The linkage interval has not been narrowed and attempts to identify the gene continue. Studying families with lymphoproliferative cancers has been a long-standing interest. We have described CLL kindreds, evaluated candidate genes (i.e. ATM), potential susceptibility markers (i.e. telomerase), anticipation (early onset of disease in familial cases) and a key prognostic factor in the familial setting (CD38 and Vh gene mutation status). Most recently we have conducted a linkage analysis on suitable CLL kindreds which identified several areas of interest for further study. We are genotyping additional families to clarify which areas of interest to pursue. We hosted an international meeting to develop a consortium to study familial CLL adn we continue to devlop these collaborations. The first effort will be to expand the linkage study in cooperation with other major groups. A new study of Waldenstrom's macroglobulinemia was also initiated and is currently in the field phase. We hope to initiate linkage studies soon. The non-Hodgkin's lymphoma families have been reactivated, and the development of another new consortium is being contemplated.